Antitumor Effects of pH-/Reduction-Responsive Fe3O4@Alginate Magnetic Nanoparticles Loaded with Doxorubicin on Subcutaneous Tumor Models of Hepatocellular Carcinoma Xenografts in BALB/c Nude Mice,ACS Applied Nano Materials

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Antitumor Effects of pH-/Reduction-Responsive Fe3O4@Alginate Magnetic Nanoparticles Loaded with Doxorubicin on Subcutaneous Tumor Models of Hepatocellular Carcinoma Xenografts in BALB/c Nude Mice
ACS Applied Nano Materials ( IF 5.3 ) Pub Date : 2021-03-23 , DOI: 10.1021/acsanm.1c00181
Na Peng _{1,

2} , Clairissa D. Corpstein ₂ , Yanlong Wang ₁ , Mingyue Yang ₁ , Chenghuan Hua ₁ , Tao Zou ₁ , Yang Cheng ₁ , Kui Wu ₁ , Yi Liu _{1,

3}

Affiliation

Superparamagnetic iron oxides (SPION-4) were modified using pH-/reduction-responsive alginate and prepared for magnetic-targeted delivery of doxorubicin (DOX) to inhibit tumor growth in hepatocellular carcinoma xenografted subcutaneous tumor of BALB/c nude mice. The release profile of DOX-loaded SPION-4 showed the best fitting in the Makoid–Banakar model with faster release rates under higher concentrations of glutathione. The introduction of disulfide bonds into SPION-4 greatly elevated its release capabilities, thus leading to high DOX concentrations in the cytoplasm and nucleus in vitro and in tumor tissues in vivo, in the presence of an external magnet. Additionally, the DOX concentration in heart tissues after being treated by DOX-loaded SPION-4 was significantly lower than that dressed with free DOX. The in vivo results showed that the DOX-loaded SPION-4-magnet group displayed the best effects on inhibiting tumor growth, with an extensively larger necrotic area and enhanced antivascular effects on the vascular endothelial growth factor and CD34 inhibition when compared to the other groups. This obvious improvement in anticancer efficacy of DOX-loaded SPION-4 supports its potential application as an effective chemotherapeutic agent for inhibiting tumor growth.

中文翻译：

pH /还原反应性Fe ₃ O ₄藻酸盐磁性纳米粒子对阿霉素/肝癌裸鼠移植瘤肝癌皮下移植瘤模型的抗肿瘤作用

使用pH- /还原反应性藻酸盐修饰超顺磁性氧化铁（SPION-4），并准备将其用于磁性靶向递送阿霉素（DOX）以抑制BALB / c裸鼠肝细胞癌异种皮下移植瘤的生长。装有DOX的SPION-4的释放曲线显示出在Makoid–Banakar模型中的最佳拟合，在较高的谷胱甘肽浓度下释放速度更快。将二硫键引入SPION-4可大大提高其释放能力，从而导致体外和体内肿瘤组织的细胞质和细胞核中的DOX浓度较高，在有外部磁铁的情况下。此外，经DOX加载的SPION-4处理后，心脏组织中的DOX浓度显着低于使用游离DOX处理的心脏组织。该体内结果显示，相比于其它基团，当装载DOX SPION -4-磁体组显示在抑制肿瘤生长，与广泛较大坏死区和增强的对血管内皮生长因子和CD34抑制抗血管作用效果最好。载有DOX的SPION-4在抗癌功效方面的这一明显改善，支持其作为抑制肿瘤生长的有效化学治疗剂的潜在应用。

更新日期：2021-04-23

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